Abstract
OBJECTIVE: This study aimed to determine whether APOA2 genotypes and saturated fatty acid (SAT) intake affect weight-loss response to healthy low-carbohydrate (HLC) and healthy low-fat (HLF) diets. METHODS: This is a secondary analysis of the Diet Intervention Examining The Factors Interacting with Treatment Success (DIETFITS) study, a 12-month randomized clinical trial of HLC or HLF diets in 609 adults aged 18 to 50 years with BMI values between 28 and 40 kg/m(2). The current study examined 3-, 6-, and 12-month weight loss in participants with different APOA2 genotypes (TT vs. C allele carriers, CT + CC) at variant rs5082 who met the SAT intake criterion of ≥22 g/day for an HLC diet and < 22 g/day for an HLF diet at all three study time points. RESULTS: Participants with the TT APOA2 genotype lost significantly more weight consistently on an HLC diet than on an HLF diet at 3, 6, and 12 months, whereas C allele carriers lost more weight only at 3 months and not at 6 or 12 months. APOA2 genotype-by-SAT intake interaction affecting weight loss was observed only at 12 months. Among participants who did not consistently meet the SAT intake criterion, there were no significant weight-loss differences among APOA2 genotypes. CONCLUSIONS: This study highlights the importance of evaluating genotype-diet interactions in weight-loss trials to better inform precision nutrition interventions. CLINICAL TRIAL REGISTRATION: NCT01826591.